Previous studies have shown that genetic factors influence not only the risk of epilepsy but also its clinical features. However, it remains unclear which individual clinical features have an inherited basis and how these characteristics might cluster as a result of a common genetic cause. We propose to systematically examine which clinical features of epilepsy best reflect differences in susceptibility, and therefore could be used to divide the epilepsies into subgroups appropriate for linkage analysis. Although some EEG abnormalities have been shown to have a genetic component, the genetic relationship between these EEG abnormalities and clinically manifest epilepsy needs further exploration. The applicant will examine the way in which generalized EEG abnormalities aggregate in families concordant or discordant for generalized or focal epilepsy to investigate how these abnormalities should best be used to define families or an individual's disease status for linkage analysis. The applicant will address the problem of phenotype definition in epilepsy in approximately 130 families containing multiple individuals with idiopathic/cryptogenic epilepsy ascertained in the Epilepsy Family Study of Columbia University. The applicants will conduct semi-structured telephone interviews and EEGs on a subgroup of these families. Their aims are to: (1) evaluate the consistency of clinical features within families, classifying by seizure type, syndrome type, specific seizure symptoms, and age at onset; (2) evaluate EEG abnormalities within families concordant and discordant for seizure type; and (3) develop an instrument to assess epilepsy severity and use this instrument to evaluate the consistency of epilepsy severity as a clinical feature within families. This applicant is trained as an academic clinical neurologist with specialization in epilepsy/clinical neurophysiology and neuroepidemiology. This grant will enable her to develop an academic career in neurology and genetic epidemiology by allowing her to (1) collaborate with neurologists and genetic epidemiologists in the Sergievsky Center, (2) learn methods of genetic epidemiology, statistical genetics, laboratory and computational techniques in molecular genetics and (3) gain independence as a clinical investigator, through the combined responsibilities of formal coursework, conferences and research. Drs. R. Ottman, W.A. Hauser, S. Hodge, T. C. Gilliam and M. Morrell will provide guidance in these endeavors.